Divalent cation induced re-entrant condensation behavior for lipopolysaccharides

Area of Science:

• Biophysics
• Computational Chemistry
• Microbiology

Background:

• Lipopolysaccharides (LPSs) are key components of Gram-negative bacteria (GNB) outer membranes.
• Divalent cations (DCs) are traditionally viewed as solely stabilizing these membranes.

Purpose of the Study:

• To investigate the complex role of divalent cations in LPS interaction and membrane stability.
• To explore the concentration-dependent effects of DCs on LPS aggregation and dissolution.

Main Methods:

• Utilized coarse-grained (CG) Martini force field for molecular dynamic (MD) simulations.
• Analyzed LPS binding free energy and LPS-LPS aggregate formation.
• Simulated a wide range of DC concentrations.

Main Results:

• Initial DC addition promotes LPS aggregation, while higher concentrations lead to dissolution.
• Observed a switch in LPS effective charge from negative to positive with increasing DC concentration.
• Demonstrated a non-monotonic dependence of LPS packing rigidity on DC concentration, exhibiting re-entrant condensation.

Conclusions:

• Divalent cations play a dual role in LPS aggregation and dissolution, challenging the traditional view.
• The discovered re-entrant condensation phenomenon in LPS offers a novel mechanism for membrane perturbation.
• Findings suggest potential for developing multivalent ion-based agents as effective GNB antibiotics.